HDAH_PSEAE
ID HDAH_PSEAE Reviewed; 380 AA.
AC Q9HXM1;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Histone deacetylase-like amidohydrolase {ECO:0000303|PubMed:27756124};
DE Short=HDAH {ECO:0000303|PubMed:27756124};
DE EC=3.5.1.- {ECO:0000269|PubMed:26956223};
DE AltName: Full=Acetylated lysine deacetylase {ECO:0000305};
DE AltName: Full=Histone deacetylase homolog PA3774 {ECO:0000303|PubMed:27951649};
GN OrderedLocusNames=PA3774 {ECO:0000312|EMBL:AAG07161.1};
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, DEACETYLASE ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1, and PA14;
RX PubMed=26956223; DOI=10.1186/s12858-016-0063-z;
RA Kraemer A., Herzer J., Overhage J., Meyer-Almes F.J.;
RT "Substrate specificity and function of acetylpolyamine amidohydrolases from
RT Pseudomonas aeruginosa.";
RL BMC Biochem. 17:4-4(2016).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH ZINC AND A
RP PHOTOSWITCHABLE LIGAND INHIBITOR, BIOTECHNOLOGY, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=27756124; DOI=10.1021/acsinfecdis.6b00148;
RA Weston C.E., Kramer A., Colin F., Yildiz O., Baud M.G., Meyer-Almes F.J.,
RA Fuchter M.J.;
RT "Toward photopharmacological antimicrobial chemotherapy using
RT photoswitchable amidohydrolase inhibitors.";
RL ACS Infect. Dis. 3:152-161(2017).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2-380 OF WILD-TYPE AND MUTANTS
RP ALA-143 AND PHE-313 IN COMPLEXES WITH ZINC; A TRIFLUOROMETHYLKETONE
RP INHIBITOR; ACETATE AND A HYDROXAMATE INHIBITOR, MUTAGENESIS OF HIS-143;
RP HIS-144 AND TYR-313, COFACTOR, AND SUBUNIT.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=27951649; DOI=10.1021/acs.biochem.6b00613;
RA Kraemer A., Wagner T., Yildiz O., Meyer-Almes F.J.;
RT "Crystal structure of a histone deacetylase homologue from Pseudomonas
RT aeruginosa.";
RL Biochemistry 55:6858-6868(2016).
CC -!- FUNCTION: Probable protein deacetylase that catalyzes deacetylation of
CC acetylated lysine residues. In vitro, exhibits high activity against
CC artificial HDAC (histone deacetylase) substrates containing acetylated
CC and trifluoroacetylated lysine residues. Is not able to deacetylate
CC acetylated polyamines. {ECO:0000269|PubMed:26956223}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:27951649};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:27951649};
CC -!- ACTIVITY REGULATION: Is inhibited by azobenzenes, stilbenes and
CC arylazopyrazoles. {ECO:0000269|PubMed:27756124}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=95 uM for Boc-Lys(Ac)-AMC {ECO:0000269|PubMed:26956223};
CC KM=21 uM for Boc-Lys(TFA)-AMC {ECO:0000269|PubMed:26956223};
CC Vmax=3.4 nmol/sec/mg enzyme with Boc-Lys(Ac)-AMC as substrate
CC {ECO:0000269|PubMed:26956223};
CC Vmax=8.6 nmol/sec/mg enzyme with Boc-Lys(TFA)-AMC as substrate
CC {ECO:0000269|PubMed:26956223};
CC -!- SUBUNIT: Homotetramer; dimer of head-to-head dimers.
CC {ECO:0000269|PubMed:27951649}.
CC -!- DISRUPTION PHENOTYPE: Growth of a mutant strain lacking this gene in
CC the presence of both acetylcadaverine and acetylputrescine is
CC comparable to growth of the wild-type. The deletion mutant strain shows
CC a 25% increase in biofilm biomass after 24 hours of incubation compared
CC to wild-type cells. {ECO:0000269|PubMed:26956223}.
CC -!- BIOTECHNOLOGY: Could be a suitable photopharmacological target for
CC photopharmacological antimicrobial chemotherapy using photoswitchable
CC inhibitors. {ECO:0000305|PubMed:27756124}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. {ECO:0000305}.
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DR EMBL; AE004091; AAG07161.1; -; Genomic_DNA.
DR PIR; D83174; D83174.
DR RefSeq; NP_252463.1; NC_002516.2.
DR RefSeq; WP_003113816.1; NZ_QZGE01000001.1.
DR PDB; 5G0X; X-ray; 1.70 A; A/C=2-380.
DR PDB; 5G0Y; X-ray; 2.29 A; A/B=2-380.
DR PDB; 5G10; X-ray; 1.71 A; A/B=2-380.
DR PDB; 5G11; X-ray; 2.48 A; A/B=2-380.
DR PDB; 5G12; X-ray; 2.02 A; A/B=2-380.
DR PDB; 5G13; X-ray; 1.99 A; A/B=2-380.
DR PDB; 5LI3; X-ray; 2.40 A; A/B=1-380.
DR PDBsum; 5G0X; -.
DR PDBsum; 5G0Y; -.
DR PDBsum; 5G10; -.
DR PDBsum; 5G11; -.
DR PDBsum; 5G12; -.
DR PDBsum; 5G13; -.
DR PDBsum; 5LI3; -.
DR AlphaFoldDB; Q9HXM1; -.
DR SMR; Q9HXM1; -.
DR STRING; 287.DR97_4095; -.
DR PaxDb; Q9HXM1; -.
DR PRIDE; Q9HXM1; -.
DR EnsemblBacteria; AAG07161; AAG07161; PA3774.
DR GeneID; 880599; -.
DR KEGG; pae:PA3774; -.
DR PATRIC; fig|208964.12.peg.3951; -.
DR PseudoCAP; PA3774; -.
DR HOGENOM; CLU_007727_8_2_6; -.
DR InParanoid; Q9HXM1; -.
DR OMA; GRAMGFC; -.
DR PhylomeDB; Q9HXM1; -.
DR BioCyc; PAER208964:G1FZ6-3845-MON; -.
DR BRENDA; 3.5.1.98; 5087.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004407; F:histone deacetylase activity; IBA:GO_Central.
DR GO; GO:0016787; F:hydrolase activity; IDA:PseudoCAP.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PRINTS; PR01270; HDASUPER.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..380
FT /note="Histone deacetylase-like amidohydrolase"
FT /id="PRO_0000439409"
FT ACT_SITE 144
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q48935"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27756124,
FT ECO:0000269|PubMed:27951649, ECO:0000312|PDB:5LI3,
FT ECO:0007744|PDB:5G0X"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27756124,
FT ECO:0000269|PubMed:27951649, ECO:0000312|PDB:5LI3,
FT ECO:0007744|PDB:5G0X"
FT BINDING 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27756124,
FT ECO:0000269|PubMed:27951649, ECO:0000312|PDB:5LI3,
FT ECO:0007744|PDB:5G0X"
FT SITE 313
FT /note="Polarizes the scissile carbonyl of the substrate"
FT /evidence="ECO:0000250|UniProtKB:Q48935"
FT MUTAGEN 143
FT /note="H->A: Loss of enzymatic activity against both
FT acetylated and trifluoroacetylated lysine substrates."
FT /evidence="ECO:0000269|PubMed:27951649"
FT MUTAGEN 144
FT /note="H->A: Loss of enzymatic activity against both
FT acetylated and trifluoroacetylated lysine substrates."
FT /evidence="ECO:0000269|PubMed:27951649"
FT MUTAGEN 313
FT /note="Y->F: Loss of enzymatic activity against acetylated
FT lysine substrate but no effect on activity with
FT trifluoroacetylated lysine substrate."
FT /evidence="ECO:0000269|PubMed:27951649"
FT MUTAGEN 313
FT /note="Y->H: Loss of enzymatic activity against acetylated
FT lysine substrate but only 15% decrease in activity against
FT trifluoroacetylated lysine substrate."
FT /evidence="ECO:0000269|PubMed:27951649"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 11..15
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 58..61
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 72..76
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 108..127
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 158..170
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 186..191
FT /evidence="ECO:0007829|PDB:5G0X"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 196..205
FT /evidence="ECO:0007829|PDB:5G0X"
FT TURN 206..212
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 250..257
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 283..300
FT /evidence="ECO:0007829|PDB:5G0X"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:5G0X"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 318..330
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 341..346
FT /evidence="ECO:0007829|PDB:5G0X"
FT HELIX 351..367
FT /evidence="ECO:0007829|PDB:5G0X"
SQ SEQUENCE 380 AA; 41049 MW; 07042D0FADED1936 CRC64;
MTRRTAFFFD ELCLWHAAGP HALTLPVGGW VQPPAAAGHA ESPETKRRLK SLLDVSGLTA
RLQLRSAPPA SDEDLLRVHP AHYLERFKAL SDAGGGSLGQ DAPIGPGSYE IARLSAGLAI
AALDAVLAGE ADNAYSLSRP PGHHCLPDQA MGFCFFANIA VAIEAAKARH GVERVAVLDW
DVHHGNGTQA IYYRRDDVLS ISLHQDGCFP PGYSGAEDIG EDRGRGFNLN VPLLPGGGHD
AYMQAMQRIV LPALERFRPQ LIVVASGFDA NAVDPLARMQ LHSDSFRAMT AMVRDAAERH
AGGRLVVVHE GGYSEAYVPF CGLAVIEELS GVRSAVRDPL RDFIELQQPN AAFRDFQRQR
LEELAAQFGL CPAQPLQAAR
